Dimethylformamide → Methyl 5-cyano-2-cyclobutyl-4-methylbenzoate

HRID 1487977Notes

Reaction equation

HRID 1487977 reaction equation
[CH:1]1([C:5]2[CH:14]=[C:13]([CH3:15])[C:12](I)=[CH:11][C:6]=2[C:7]([O:9][CH3:10])=[O:8])[CH2:4][CH2:3][CH2:2]1.[CH3:17][N:18](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:17]([C:12]1[C:13]([CH3:15])=[CH:14][C:5]([CH:1]2[CH2:4][CH2:3][CH2:2]2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])#[N:18]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68288304Methyl 2-cyclobutyl-5-iodo-4-methylbenzoate2×

Product 1

HCID 68288958Methyl 5-cyano-2-cyclobutyl-4-methylbenzoateYield 96%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 2-cyclobutyl-5-iodo-4-methylbenzoate (compound 89.3, 3.0 g, 9.1 mmol), Zn(CN)2 (2.3 g, 19.6 mmol) and Pd(PPh3)4 (0.55 g, 0.47 mmol) in DMF (50 mL) was degassed and the system was charged with argon. The mixture was heated at 100° C. overnight, then cooled to room temperature. The mixture was quenched with saturated aqueous FeSO4 (20 mL), then diluted with EtOAc (200 mL). The solids were removed by filtration through Celite® and the filtrate was partitioned between water and EtOAc. The organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1) to yield 2.0 g (96%) of the title compound. 1H NMR (400 MHz, Chloroform-d) δ 8.03 (s, 1H), 7.34 (s, 1H), 4.26-4.13 (m, 1H), 3.89 (s, 3H), 2.59 (s, 3H), 2.46-2.32 (m, 2H), 2.16-1.98 (m, 3H), 1.90-1.78 (m, 1H).

Workup

  1. customwas degassed
  2. additionthe system was charged with argon
  3. temperaturecooled to room temperature
  4. customThe mixture was quenched with saturated aqueous FeSO4 (20 mL)
  5. additiondiluted with EtOAc (200 mL)
  6. customThe solids were removed by filtration through Celite®
  7. customthe filtrate was partitioned between water and EtOAc
  8. washThe organic layer was washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1)

Sources & evidence

ORD record
ord-ddacfe6829ec4412981f3060526bdec9
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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